The 2019 World Health Organization Classification of appendiceal, colorectal and anal canal tumours: an update and critical assessment

Ahadi, Mahsa; Sokolova, Anna; Brown, Ian; Chou, Angela; Gill, Anthony J.

doi:10.1016/j.pathol.2020.10.010

Cited by 77 publications

(86 citation statements)

References 46 publications

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“…1,4 In such situation, an immunohistochemical staining using the BRAF V600E mutation-specific VE1 antibody or molecular studies looking for KRAS and BRAF mutations might be necessary to solve these morphologic ambiguities. 4 Likewise, a serrated architecture can be occasionally seen in low grade appendiceal mucinous neoplasms (LAMNs). 1 However, in contrast to SLs and SPs, these challenging LAMNs display at least some villiform areas with long filiform villi without serration.…”

Section: Discussionmentioning

confidence: 99%

“…1 It should be noted, however, that dysplasia in SLs and SPs is histologically heterogeneous and occasionally difficult to grade reliably. 3 , 4 Moreover, some subtle patterns of dysplasia, especially the so-called minimal deviation dysplasia, may be particularly difficult to recognize morphologically. 3 Fortunately, this deceptive form of dysplasia is often associated with loss of MLH1 expression, which allows its identification by immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

“…3 In all likelihood, dysplasia arising in SLs and SPs indicates an “advanced” lesion with a higher risk of progression to carcinoma, which necessitates both complete excision and closer surveillance. 3 , 4…”

Section: Discussionmentioning

confidence: 99%

“…3 As a result, the absence of dysplastic features, the maintained expression of MLH1 by neoplastic cells and the absence of methylation at the MLH1 promoter in our patient most likely indicate an “early” form of SSL, as defined in some studies. 3 , 4 , 16…”

Section: Discussionmentioning

confidence: 99%

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Sessile Serrated Lesion of the Appendix in a Teenage Girl

et al. 2021

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According to the literature, serrated lesions and polyps of the appendix are extremely rare in children or teenagers. Herein, we present the pathologic and molecular features of a sessile serrated lesion (SSL) that was incidentally found in the appendix of a teenage girl. Our findings not only illustrate that appendiceal SSL may occur in young patients such as teenagers but also confirm further that BRAF V600E mutation may be found in a subset of these neoplastic lesions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Sessile Serrated Lesion of the Appendix in a Teenage Girl

et al. 2021

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“…None of the patients had metastatic tumors. Among them, one patient had stage 1 CRC, two patients had stage 2 CRC and the other two patients had stage 3 CRC according to the World Health Organization Classification ( 31 ). The tissues were immediately frozen in dry ice and stored at −80°C until further use.…”

Section: Methodsmentioning

confidence: 99%

RNA m⁶A methyltransferase METTL3 promotes colorectal cancer cell proliferation and invasion by regulating Snail expression

et al. 2021

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Nitrogen 6-methyladenosine (m 6 A) is the result of methylation of nitrogen-6 on adenosine, and is the most abundant chemical modification of eukaryotic mRNA. Dysregulation of m 6 A methylation has been implicated in cancer development and progression through various mechanisms. This type of methylation is primarily regulated by methyltransferase-like 3 (METTL3). However, the molecular mechanisms underlying the role of METTL3 in colorectal cancer (CRC) have not been extensively elucidated. The present study explored m 6 A modification and the underlying mechanism of m 6 A, which serve regulatory roles in the development of CRC. It was found that METTL3 is upregulated in CRC cell lines and tissues, and its expression positively correlated with poor overall survival (OS). Mechanistically, the present study demonstrated that METTL3 methylates Snail mRNA, thus stabilizing it to promote CRC malignancy. The present findings indicate that m 6 A modification is involved in CRC tumorigenesis, and highlight its potential as a therapeutic target against CRC.

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Transcriptome of sessile serrated adenoma/polyps is associated with MSI‐high colorectal cancer and decreased expression of CDX2

Yamamichi

2022

Cancer Medicine

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The objective of this study was to elucidate the molecular background of sessile serrated adenoma/polyp (SSA/P) endoscopically resected with comprehensive gene expression analysis. Gene expression profiling was performed for 10 tumor‐normal pairs of SSA/P. Cluster analysis, gene set enrichment analysis (GSEA), and consensus molecular subtype (CMS) classification of colorectal cancer (CRC) were applied to our transcriptome analysis. Unsupervised cluster analysis showed that the gene expression profile of SSA/Ps is different from that of adjacent normal epithelial cells, even in the very early stage of tumorigenesis. According to the CMS classification, our microarray data indicated that SSA/Ps were classified as CMS1. GSEA demonstrated a strong association between SSA/P and microsatellite instability‐high (MSI‐H) CRC (p < 10−5). Transcriptome analysis of five MSI‐related genes (MSH2, MSH6, MLH1, PMS1, and PMS2) and five CRC‐related genes (BRAF, KRAS, APC, TP53, and CDX2) showed that CDX2 expression was most severely decreased in SSA/P. Immunohistochemical staining confirmed that CDX2 protein was reduced compared with the surrounding mucosa. Direct sequencing of the BRAF gene showed that the BRAF V600E mutation was detected in only nine of 36 cases. In a mouse model, BRAF, APC, or CDX2 deficiency indicated that the gene expression pattern with loss of CDX2 is more similar to our SSA/Ps compared with those induced by BRAF or APC mutation. Transcriptome analysis of SSA/Ps showed characteristic gene expression with a strong resemblance to MSI‐H CRC. Downregulation of CDX2 expression is an essential molecular mechanism involved in the initial stage of SSA/P tumorigenesis. (UMIN000027365).

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The 2019 World Health Organization Classification of appendiceal, colorectal and anal canal tumours: an update and critical assessment

Cited by 77 publications

References 46 publications

Sessile Serrated Lesion of the Appendix in a Teenage Girl

Sessile Serrated Lesion of the Appendix in a Teenage Girl

RNA m⁶A methyltransferase METTL3 promotes colorectal cancer cell proliferation and invasion by regulating Snail expression

Transcriptome of sessile serrated adenoma/polyps is associated with MSI‐high colorectal cancer and decreased expression of CDX2

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The 2019 World Health Organization Classification of appendiceal, colorectal and anal canal tumours: an update and critical assessment

Cited by 77 publications

References 46 publications

Sessile Serrated Lesion of the Appendix in a Teenage Girl

Sessile Serrated Lesion of the Appendix in a Teenage Girl

RNA m6A methyltransferase METTL3 promotes colorectal cancer cell proliferation and invasion by regulating Snail expression

Transcriptome of sessile serrated adenoma/polyps is associated with MSI‐high colorectal cancer and decreased expression of CDX2

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RNA m⁶A methyltransferase METTL3 promotes colorectal cancer cell proliferation and invasion by regulating Snail expression